Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery
The aim of this study was to develop high load-capacity antibubbles that can be visualized using diagnostic ultrasound and the encapsulated drug can be released and delivered using clinically translatable ultrasound.The antibubbles were developed by optimising a silica nanoparticle stabilised double...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Ultrasonics Sonochemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1350417722000797 |
| _version_ | 1818393849528057856 |
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| author | Spiros Kotopoulis Christina Lam Ragnhild Haugse Sofie Snipstad Elisa Murvold Tæraneh Jouleh Sigrid Berg Rune Hansen Mihaela Popa Emmet Mc Cormack Odd Helge Gilja Albert Poortinga |
| author_facet | Spiros Kotopoulis Christina Lam Ragnhild Haugse Sofie Snipstad Elisa Murvold Tæraneh Jouleh Sigrid Berg Rune Hansen Mihaela Popa Emmet Mc Cormack Odd Helge Gilja Albert Poortinga |
| author_sort | Spiros Kotopoulis |
| collection | DOAJ |
| description | The aim of this study was to develop high load-capacity antibubbles that can be visualized using diagnostic ultrasound and the encapsulated drug can be released and delivered using clinically translatable ultrasound.The antibubbles were developed by optimising a silica nanoparticle stabilised double emulsion template.We produced an emulsion with a mean size diameter of 4.23 ± 1.63 µm where 38.9 ± 3.1% of the droplets contained a one or more cores. Following conversion to antibubbles, the mean size decreased to 2.96 ± 1.94 µm where 99% of antibubbles were <10 µm. The antibubbles had a peak attenuation of 4.8 dB/cm at 3.0 MHz at a concentration of 200 × 103 particles/mL and showed distinct attenuation spikes at frequencies between 5.5 and 13.5 MHz. No increase in subharmonic response was observed for the antibubbles in contrast to SonoVue®. High-speed imaging revealed that antibubbles can release their cores at MIs of 0.6. In vivo imaging indicated that the antibubbles have a long half-life of 68.49 s vs. 40.02 s for SonoVue®. The antibubbles could be visualised using diagnostic ultrasound and could be disrupted at MIs of ≥0.6. The in vitro drug delivery results showed that antibubbles can significantly improve drug delivery (p < 0.0001) and deliver the drug within the antibubbles. In conclusion antibubbles are a viable concept for ultrasound guided drug delivery. |
| first_indexed | 2024-12-14T05:51:51Z |
| format | Article |
| id | doaj.art-5d47ca571b354eb7ac5fe0777027c211 |
| institution | Directory Open Access Journal |
| issn | 1350-4177 |
| language | English |
| last_indexed | 2024-12-14T05:51:51Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ultrasonics Sonochemistry |
| spelling | doaj.art-5d47ca571b354eb7ac5fe0777027c2112022-12-21T23:14:42ZengElsevierUltrasonics Sonochemistry1350-41772022-04-0185105986Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug deliverySpiros Kotopoulis0Christina Lam1Ragnhild Haugse2Sofie Snipstad3Elisa Murvold4Tæraneh Jouleh5Sigrid Berg6Rune Hansen7Mihaela Popa8Emmet Mc Cormack9Odd Helge Gilja10Albert Poortinga11Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Neoety AS, Kløfta, Norway; Corresponding author.Department of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, Norway; Department of Quality and Development, Hospital Pharmacies Enterprise in Western Norway, Bergen, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway; Cancer Clinic, St. Olav’s Hospital, Trondheim, Norway; Department of Physics, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; KinN Therapeutics, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, NorwayDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Health Research, SINTEF Digital, Trondheim, NorwayDepartment of Clinical Science, University of Bergen, Bergen, Norway; CCBIO, Department of Clinical Science, University of Bergen, NorwayKinN Therapeutics, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, NorwayPolymer Technology, Eindhoven University of Technology, Eindhoven, the NetherlandsThe aim of this study was to develop high load-capacity antibubbles that can be visualized using diagnostic ultrasound and the encapsulated drug can be released and delivered using clinically translatable ultrasound.The antibubbles were developed by optimising a silica nanoparticle stabilised double emulsion template.We produced an emulsion with a mean size diameter of 4.23 ± 1.63 µm where 38.9 ± 3.1% of the droplets contained a one or more cores. Following conversion to antibubbles, the mean size decreased to 2.96 ± 1.94 µm where 99% of antibubbles were <10 µm. The antibubbles had a peak attenuation of 4.8 dB/cm at 3.0 MHz at a concentration of 200 × 103 particles/mL and showed distinct attenuation spikes at frequencies between 5.5 and 13.5 MHz. No increase in subharmonic response was observed for the antibubbles in contrast to SonoVue®. High-speed imaging revealed that antibubbles can release their cores at MIs of 0.6. In vivo imaging indicated that the antibubbles have a long half-life of 68.49 s vs. 40.02 s for SonoVue®. The antibubbles could be visualised using diagnostic ultrasound and could be disrupted at MIs of ≥0.6. The in vitro drug delivery results showed that antibubbles can significantly improve drug delivery (p < 0.0001) and deliver the drug within the antibubbles. In conclusion antibubbles are a viable concept for ultrasound guided drug delivery.http://www.sciencedirect.com/science/article/pii/S1350417722000797UltrasoundMicrobubblesAntibubbleTargeted drug deliverySonoporation |
| spellingShingle | Spiros Kotopoulis Christina Lam Ragnhild Haugse Sofie Snipstad Elisa Murvold Tæraneh Jouleh Sigrid Berg Rune Hansen Mihaela Popa Emmet Mc Cormack Odd Helge Gilja Albert Poortinga Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery Ultrasonics Sonochemistry Ultrasound Microbubbles Antibubble Targeted drug delivery Sonoporation |
| title | Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery |
| title_full | Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery |
| title_fullStr | Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery |
| title_full_unstemmed | Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery |
| title_short | Formulation and characterisation of drug-loaded antibubbles for image-guided and ultrasound-triggered drug delivery |
| title_sort | formulation and characterisation of drug loaded antibubbles for image guided and ultrasound triggered drug delivery |
| topic | Ultrasound Microbubbles Antibubble Targeted drug delivery Sonoporation |
| url | http://www.sciencedirect.com/science/article/pii/S1350417722000797 |
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